The histone fold: a ubiquitous architectural motif utilized in DNA compaction and protein dimerization.

The histones of all eukaryotes show only a low degree of primary structure homology, but our earlier crystallographic results defined a three-dimensional structural motif, the histone fold, common to all core histones. We now examine the specific architectural patterns within the fold and analyze the nature of the amino acid residues within its functional segments. The histone fold emerges as a fundamental protein dimerization motif while the differentiations of the tips of the histone dimers appear to provide the rules of core octamer assembly and the basis for nucleosome regulation. We present evidence for the occurrence of the fold from archaebacteria to mammals and propose the use of this structural motif to define a distinct family of proteins, the histone fold superfamily. It appears that evolution has conserved the conformation of the fold even through variations in primary structure and among proteins with various functional roles.

Carbohydrate gluing, an architectural mechanism in the supramolecular structure of an annelid giant hemoglobin.

We report a carbohydrate-dependent supramolecular architecture in the extracellular giant hemoglobin (Hb) from the marine worm Perinereis aibuhitensis; we call this architectural mechanism carbohydrate gluing. This study is an extension of our accidental discovery of deterioration in the form of the Hb caused by a high concentration of glucose. The giant Hbs of annelids are natural supramolecules consisting of about 200 polypeptide chains that associate to form a double-layered hexagonal structure. This Hb has 0.5% (wt) carbohydrates, including mannose, xylose, fucose, galactose, glucose, N-acetylglucosamine (GlcNAc), and N-acetylgalactosamine (GalNAc). Using carbohydrate-staining assays, in conjunction with two-dimensional polyacrylamide gel electrophoresis, we found that two types of linker chains (L1 and L2; the nomenclature of the Hb subunits followed that for another marine worm, Tylorrhynchus heterochaetus) contained carbohydrates with both GlcNAc and GalNAc. Furthermore, two types of globins (a and A) have only GlcNAc-containing carbohydrates, whereas the other types of globins (b and B) had no carbohydrates. Monosaccharides including mannose, fucose, glucose, galactose, GlcNAc, and GalNAc reversibly dissociated the intact form of the Hb, but the removal of carbohydrate with N-glycanase resulted in irreversible dissociation. These results show that carbohydrate acts noncovalently to glue together the components to yield the complete quaternary supramolecular structure of the giant Hb. We suggest that this carbohydrate gluing may be mediated through lectin-like carbohydrate-binding by the associated structural chains ("linkers").

Older plasma lipoproteins are more susceptible to oxidation: a linking mechanism for the lipid and oxidation theories of atherosclerotic cardiovascular disease.

Increases in plasma cholesterol are associated with progressive increases in the risk of atherosclerotic cardiovascular disease. In humans plasma cholesterol is contained primarily in apolipoprotein B-based low density lipoprotein (LDL). Cells stop making the high-affinity receptor responsible for LDL removal as they become cholesterol replete; this slows removal of LDL from plasma and elevates plasma LDL. As a result of this delayed uptake, hypercholesterolemic individuals not only have more LDL but have significantly older LDL. Oxidative modification of LDL enhances their atherogenicity. This study sought to determine whether increased time spent in circulation, or aging, by lipoprotein particles altered their susceptibility to oxidative modification. Controlled synchronous production of distinctive apolipoprotein B lipoproteins (yolk-specific very low density lipoproteins; VLDLy) with a single estrogen injection into young turkeys was used to model LDL aging in vivo. VLDLy remained in circulation for at least 10 days. Susceptibility to oxidation in vitro was highly dependent on lipoprotein age in vivo. Oxidation, measured as hexanal release from n-6 fatty acids in VLDLy, increased from 13.3 +/- 5.5 nmol of 2-day-old VLDLy per ml, to 108 +/- 17 nmol of 7-day-old VLDLy per ml. Oxidative instability was not due to tocopherol depletion or conversion to a more unsaturated fatty acid composition. These findings establish mathematically describable linkages between the variables of LDL concentration and LDL oxidation. The proposed mathematical models suggest a unified investigative approach to determine the mechanisms for acceleration of atherosclerotic cardiovascular disease risk as plasma cholesterol rises.

Re-Examining the Stop-Signal Task to Test Competing Theories of AD/HD

The current study tested two competing models of Attention-Deficit/Hyperactivity Disorder (AD/HD), the inhibition and state regulation theories, by conducting fine-grained analyses of the Stop-Signal Task and another putative measure of behavioral inhibition, the Gordon Continuous Performance Test (G-CPT), in a large sample of children and adolescents. The inhibition theory posits that performance on these tasks reflects increased difficulties for AD/HD participants to inhibit prepotent responses. The model predicts that putative stop-signal reaction time (SSRT) group differences on the Stop-Signal Task will be primarily related to AD/HD participants requiring more warning than control participants to inhibit to the stop-signal and emphasizes the relative importance of commission errors, particularly "impulsive" type commissions, over other error types on the G-CPT. The state regulation theory, on the other hand, proposes response variability due to difficulties maintaining an optimal state of arousal as the primary deficit in AD/HD. This model predicts that SSRT differences will be more attributable to slower and/or more variable reaction time (RT) in the AD/HD group, as opposed to reflecting inhibitory deficits. State regulation assumptions also emphasize the relative importance of omission errors and "slow processing" type commissions over other error types on the G-CPT. Overall, results of Stop-Signal Task analyses were more supportive of state regulation predictions and showed that greater response variability (i.e., SDRT) in the AD/HD group was not reducible to slow mean reaction time (MRT) and that response variability made a larger contribution to increased SSRT in the AD/HD group than inhibitory processes. Examined further, ex-Gaussian analyses of Stop-Signal Task go-trial RT distributions revealed that increased variability in the AD/HD group was not due solely to a few excessively long RTs in the tail of the AD/HD distribution (i.e., tau), but rather indicated the importance of response variability throughout AD/HD group performance on the Stop-Signal Task, as well as the notable sensitivity of ex-Gaussian analyses to variability in data screening procedures. Results of G-CPT analyses indicated some support for the inhibition model, although error type analyses failed to further differentiate the theories. Finally, inclusion of primary variables of interest in exploratory factor analysis with other neurocognitive predictors of AD/HD indicated response variability as a separable construct and further supported its role in Stop-Signal Task performance. Response variability did not, however, make a unique contribution to the prediction of AD/HD symptoms beyond measures of motor processing speed in multiple deficit regression analyses. Results have implications for the interpretation of the processes reflected in widely-used variables in the AD/HD literature, as well as for the theoretical understanding of AD/HD.

Nuclear Architecture: Perceptions of Architectural Technology

In this paper we explore the implications of pluralist curricula for architectural technology. This includes the potential effects on strengthening the identity of the architectural technology profession and the academic development of the discipline. This latter relies, arguably, on research being explicit in CIAT’s eight mandatory threshold standards. This work concentrates on one of the Chartered Institute of Architectural Technologist’s (CIATS’s) key subjects; 'design', defined as detail design for the architectural technologist. In postulating a philosophy of architectural technology epistemology with a focus on detail design, the pedagogy of architectural detailing in practice and academia is investigated: the associated roles of creativity and conditioning are explored. The interrelationship between conceptual design and construction processes in practice is outlined, identifying the role of the detail design specialist (architectural technologist) in the management of design and production information. Thus is identified the future architectural technologists’ specialisation of nuclear architecture: the total quality construction created by quality of thinking which permeates from and to detail design for assembly/disassembly and production within a collaboratively mechanised AEC team. A theory of nuclear architecture and an associated approach to detail design pedagogy are postulated, aiming to promote a revised perception of the definition of design for the architectural technologist. How this theory can be applied to the creation of a paradigmatic student project, themed on designing for disassembly as a key future focus of ‘Healthy Building’ design is introduced for future exploration. This future research into detail design, the authors propose, should be predicated on the appropriate methodology related to the epistemology of a design-based area of the architectural technology discipline. The roles of Professional, Statutory and Regulatory Bodies (PSRB) in the evaluation and subsequent dissemination of this detail design pedagogy, with the aim of strengthening the architectural technology discipline are emphasised.

Architectural Technology and the BIM Acronym 3: Getting to Grips with BIM

Among Small and Medium Sized Enterprises (SMEs) in particular, the UK Government’s ambitions regarding BIM uptake and diffusion across the construction sector may be tempered by a realpolitik shaped in part by interactions between the industry, Higher Education (HE) and professional practice. That premise also has a global perspective. Building on the previous 2 papers, Architectural technology and the BIM Acronym 1 and 2, this third iteration is a synthesis of research and investigations carried out over a number of years directly related to the practical implementation of BIM and its impact upon BE SMEs. First challenges, risks and potential benefits for SMEs and micros in facing up to the necessity to engage with digital tools in a competitive and volatile marketplace are discussed including tailoring BIM to suit business models, and filtering out achievable BIM outcomes from generic and bespoke aspects of practice. Second the focus is on setting up and managing teams engaging with BIM scenarios, including the role of clients; addresses a range of paradigms including lonely BIM and collaborative working. The significance of taking a whole life view with BIM is investigated including embedding soft landings principles into project planning and realisation. Thirdly procedures for setting up and managing common data environments are identified and the value of achieving smooth information flow is addressed. The overall objective of this paper is to provide SMEs with a practical strategy to develop a toolkit to BIM implementation.

The Influence of Space Layout, Technology and Teaching Approach on Student Learning: An Architectural Technology Perspective

Some would argue that there is a need for the traditional lecture format to be rethought in favour of a more active approach. However, this must form part of a bipartite strategy, considered in conjunction with the layout of any new space to facilitate alternative learning and teaching methods. With this in mind, this paper begins to examine the impact of the learning environment on the student learning experience, specifically focusing on students studying on the Architectural Technology and Management programme at Ulster University. The aim of this study is two-fold: to increase understanding of the impact of learning space layout, by taking a student centered approach; and to gain an appreciation of how technology can impact upon the learning space. The study forms part of a wider project being undertaken at Ulster University known as the Learning Landscape Transition Project, exploring the relationship between learning, teaching and space layout. Data collection was both qualitative and quantitative, with use of a case study supported by a questionnaire based on attitudinal scaling. A focus group was also used to further analyse the key trends resulting from the questionnaire. The initial results suggest that the learning environment, and the technology within it, can not only play an important part in the overall learning experience of the student, but also assist with preparation for the working environment to be experienced in professional life.

Differences and connections: beyond universal theories in planning, urban, and heritage studies

The annual Young Academics network of the Association of European School of Planning (AESOP YA) conference, entitled Differences and Connections, was held for the first time in a Southern Italian city, Palermo, Italy, during 23–26 March 2015. The call for papers attracted a wide range of authors within the field of planning and other related fields. Forty-five contributions by young academic scholars, representing 19 countries, were selected by the conference scientific committee to critically explore the themes of the conference.

Determinants of Financial Capital Use: Review of theories and implications for rural businesses. Factor Markets Working Paper No. 19, February 2012

This paper presents a review of financial economics literature and offers a comprehensive discussion and systematisation of determinants of financial capital use. In congruence with modern financial literature, it is acknowledged here that real and financial capital decisions are interdependent. While the fundamental role of the (unconstrained) demand for real capital in the demand for finance is acknowledged, the deliverable focuses on three complementary categories of the determinants of financial capital use: i) capital market imperfections; ii) factors mitigating these imperfections or their impacts; and iii) firm- and sector-related factors, which alter the severity of financial constraints and their effects. To address the question of the optimal choice of financial instruments, theories of firm capital structure are reviewed. The deliverable concludes with theory-derived implications for agricultural and non-agricultural rural business’ finance.

A Unified Approach to Automatic Testing of Architectural Constraints

Architectural decisions are often encoded in the form of constraints and guidelines. Non-functional requirements can be ensured by checking the conformance of the implementation against this kind of invariant. Conformance checking is often a costly and error-prone process that involves the use of multiple tools, differing in effectiveness, complexity and scope of applicability. To reduce the overall effort entailed by this activity, we propose a novel approach that supports verification of human- readable declarative rules through the use of adapted off-the-shelf tools. Our approach consists of a rule specification DSL, called Dicto, and a tool coordination framework, called Probo. The approach has been implemented in a soon to be evaluated prototype.

On the Evaluation of a DSL for Architectural Consistency Checking

Software architecture erodes over time and needs to be constantly monitored to be kept consistent with its original intended design. Consistency is rarely monitored using automated techniques. The cost associated to such an activity is typically not considered proportional to its benefits. To improve this situation, we propose Dicto, a uniform DSL for specifying architectural invariants. This language is designed to reduce the cost of consistency checking by offering a framework in which existing validation tools can be matched to newly-defined language constructs. In this paper we discuss how such a DSL can be qualitatively and qualitatively evaluated in practice.